Iron-catalyzed reactions

A remarkable feature of the Birch reduction of estradiol 3-methyl ether derivatives, as well as of other metal-ammonia reductions, is the extreme rapidity of reaction. Sodium and -butyl alcohol, a metal-alcohol combination having a comparatively slow rate of reduction, effects the reduction of estradiol 3-methyl ether to the extent of 96% in 5 minutes at —33° lithium also effects complete reduction under the same conditions as is to be expected. Shorter reaction times were not studied. At —70°, reduction with sodium occurs to the extent of 56 % in 5 minutes, although reduction with lithium is virtually complete (96%) in the same time. (The slow rates of reduction of compounds of the 5-methoxytetralin type is exemplified by 5-methoxy-tetralin itself with sodium and f-butyl alcohol reduction occurs to the extent of only 50% in 6 hours vs. 99+% with lithium.) The iron catalyzed reaction of sodium with alcohols must be very fast since it competes so well with the rapid Birch reduction. One cannot compensate for the presence of iron in a Birch reduction mixture containing sodium by adding additional metal to extend the reaction time. The iron catalyzed sodium-alcohol reaction is sufficiently rapid that the aromatic steroid still remains largely unreduced. 

Most iron-catalyzed reactions proceed at unprecedentedly high rates and are finished within a few minutes even when carried out at or below ambient temperature. 

When applied to polyfunctional substrates, iron catalyzed reactions allow either for selective, exhaustive, or consecutive cross-coupling processes to be carried out in "one pot."... 

The chemistry of iron has been reviewed in COMC (1982) and COMC (1995)312-314 as well as in Comprehensive Coordination Chemistry 7/.315 More recent reviews cover iron-catalyzed transformations with samarium(ll) iodide,18d the chemistry of tricarbonyliron-diene complexes,316 and iron-catalyzed reactions in organic synthesis in general.317... 

The superoxide anion radical and hydrogen peroxide are not particularly harmful to cells. It is the product of hydrogen peroxide decomposition, the hydroxyl radical (HO ), that is responsible for most of the cytotoxicity of oxygen radicals. The reaction can he catalyzed hy several transition metals, including copper, manganese, cohalt, and iron, of which iron is the most ahimdant in the human body (Reaction 2 also called the Fenton reaction). To avoid iron-catalyzed reactions, iron is transported and stored chiefly as Fe(III), although redox active iron can be formed in oxidative reactions, and Fe(III) can be reduced by semiquinone radicals (Reaction 3). 

An iron-catalyzed reaction between bis(2,4-dimethoxyphenyl)sulfide and sulfur monochloride in dilute chloroform led to a mixture of metacyclophanes in... 

The iron-catalyzed reaction of 1,3-dimethoxybenzene with sulfur monochloride in dilute chloroform gave two polysulfur heterocycles 245 and 246 with six sulfur atoms in the molecule, yields were very low (1979JCS(P1)1712 Scheme 131). 

Table 8.6 shows two proposed mechanisms for the iron-catalyzed reaction at high acidities, in the pH range from 0 to 3.6. The recommended rate expression is given by (Martin, 1994) ... 

Fe(III) refers to the sum of all three-valent iron in solution, i.e., Fe(III) = Fe3++ FeOH2+ + Fe(OH)2+ + FeOHSO-, + FeSO + etc. Thus the rate of the iron-catalyzed reaction in the low-pH region decreases with increasing [H + ], This means that it shows the behavior depicted in Fig. 8.9a i.e., it is self-quenching. That is, as S(IV) is oxidized to the acid, the pH falls and the rate also decreases. 

Iron-Catalyzed Reactions of Grignard Reagents TABLE 1. Regioselective preparation of trimethylsilyl enol ether... 

Recently, Fu and coworkers have shown that secondary alkyl halides do not react under palladium catalysis since the oxidative addition is too slow. They have demonstrated that this lack of reactivity is mainly due to steric effects. Under iron catalysis, the coupling reaction is clearly less sensitive to such steric influences since cyclic and acyclic secondary alkyl bromides were used successfully. Such a difference could be explained by the mechanism proposed by Cahiez and coworkers (Figure 2). Contrary to Pd°, which reacts with alkyl halides according to a concerted oxidative addition mechanism, the iron-catalyzed reaction could involve a two-step monoelectronic transfer. 

VII. APPLICATIONS OF IRON-CATALYZED REACTIONS OF GRIGNARD REAGENTS IN ORGANIC SYNTHESIS... 

These last years, several syntheses of natural products using an iron-catalyzed reaction of Grignard reagents have been published. In 1969, Meinwald and Hendry used the reaction discovered by Kharasch and Tawney to prepare an allenic sesquiterpenoid isolated from the grasshopper Romalea Microptera (Scheme 61). 

The difficulty in removing metal residues from the product induced the search for iron-catalyzed reactions [77]. However, iron complexes can play different roles in catalytic processes ... 

This section provides only a brief insight into iron-catalyzed reactions. Iron complexes as catalytically active species undergo typical steps of transition metal catalysis... 

Another successful iron-catalyzed reaction is sulfoxidation, consisting of the use of the binary catalyst Fe(N03)3 -9H20-FeBr3.This system was able to catalyze efficiently the oxidation of sulfides at room temperature in MeCN under air (Table 3.8) [159]. 

Transition metal-catalyzed cross-coupling reactions between vinyl organometallic compounds and unactivated alkyl halides that can be usually performed with palladium, nickel and cobalt are of particular synthetic interest [37-39]. Recently, the groups of Cahiez [48] and Cossy [49] concurrently reported the first iron-catalyzed reaction of alkenyl Grignard compounds with primary and secondary alkyl halides (X=Br, I) (Scheme 5.15). The two protocols basically differ in the iron source... 

Review of iron-catalyzed reactions in organic synthesis Bolm, C. Legros, J. ... 

CpFe(CO)2(thf)]+, is generated by protonation of the respective iron-methyl complex with HBF4 in THF solution. Iron-catalyzed reactions of phenyldiazomethane with aldehydes resulted in mixtures of ketones and epoxides [29]. 

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